resistance and second generation tyrosine kinase inhibitors

... pathways…………………………… 1.2 The role of tyrosine kinases in cancer……………………………………… 1.3 Tyrosine kinase inhibitors as therapeutic agents in cancer………………… 1.4 Clinical resistance to tyrosine kinase inhibitors ………………………… ... (SH2) and protein tyrosine- binding (PTB) domains4 Two families of tyrosine kinases exist within cells They are the receptor tyrosine kinases as well as the non-receptor tyrosine kinases Receptor tyrosine ... polymorphism on resistance to tyrosine kinase inhibitors ………………………… 42 3.1 Introduction……………………………………………………………… 43 iii 3.2 The BIM deletion polymorphism mediates resistance to tyrosine kinase inhibitors...

Ngày tải lên: 10/09/2015, 09:04

... ⁄ and the PI3K ⁄ Akt pathways results, in turn, in the inactivation of pro-apoptotic Bcl-2 proteins (e.g PUMA, Bax, Bim and Bad), Fas, and CDK inhibitors (e.g p27KIP1, p21WAF1 and p15INK4b), and ... JNK and mitogen-activated protein kinase phosphatase-1 The activity of JNK, one of the MAPKs, is tightly controlled by both protein kinases, such as MAPK kinase (MKK4) or MAPK kinase (MKK7) and ... protein kinase, and Pak1 pathways and invasiveness of human cutaneous squamous cancer cells by the tyrosine kinase inhibitor ZD1839 (Iressa) Mol Cancer Ther 2, 345–351 Adam L, Vadlamudi R, Mandal...

Ngày tải lên: 16/02/2014, 09:20

... prostate and SV 6720 (320) yes dysuria and nocturia and urinary frequency 2, anorexia 1, diarrhea 1, hematochezia 18 prostate and SV 8000 (200) yes nocturia and urinary frequency 7 prostate and SV ... darunavir and lopinavir (7 [33%] each), atazanavir (5 [24%]), and only one [5%] patient received nelfinavir (Table and 2) Toxicities Follow-up and observed toxicities are presented in Table and The ... Pelvis dysuria and nocturia 2, urinary retention 1, constipation fatigue 2, anorexia 1, dermatitis 8c Pelvis 13 Brain 3780 and 1400 HDR (180 and 700 HDR) 3000 and 1200 IORT (200 and 1200 HDR)...

Ngày tải lên: 09/08/2014, 09:20

... Gas6 and protein S Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily Febs J 2006, 273:5231-5244 Stenhoff J, Dahlbäck B, Hafizi S: Vitamin K-dependent Gas6 activates ERK kinase ... tyrosine kinases Nat Immunol 2006, 7:747-754 doi:10.1186/cc9233 Cite this article as: Ekman et al.: Plasma concentrations of Gas6 (growth arrest specific protein 6) and its soluble tyrosine kinase ... cell- and tissue-types may be the source of the sAxl in sepsis Both Axl and Mer have been shown to be shed under the influence of PMA and LPS [10,19] Gas6 correlates with IL-6, procalcitonin and...

Ngày tải lên: 13/08/2014, 21:21

... Introduction to tyrosine kinase inhibitors 1.2 Common toxicities associated with tyrosine kinase inhibitors 1.3 Inter-patient variability in exposure of tyrosine kinase inhibitors ... of tyrosine kinase inhibitors 110 5.3.2 Potential effect of enzyme inducer/inhibitor on pharmacokinetics of tyrosine kinase inhibitors 113 5.3.3 Effect of tyrosine kinase inhibitors ... Understanding tyrosine kinase inhibitor associated toxicities: a focus on hepatotoxicity 132 6.1 Hepatotoxicity with tyrosine kinase inhibitors 132 6.2 Risk of tyrosine kinase...

Ngày tải lên: 09/09/2015, 08:14

... expands the boundaries of signalling mediators, and it is therefore not unlikely that Sky and Mer could be involved in Table Affinities of Gas6 and protein S for Axl, Sky and Mer RTKs within and ... gene and receptor tyrosine kinases Axl and Sky in human uterine leiomyoma Mol Hum Reprod 9, 701–707 Sun WS, Fujimoto J & Tamaya T (2003) Coexpression of growth arrest-specific gene and receptor tyrosine ... liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control EMBO J 24, 4260–4270 60 Heiring C, Dahlback B & Muller YA (2004) Ligand recognition and homophilic interactions...

Ngày tải lên: 19/02/2014, 05:20

... °C and capillary and cone voltages of 4230 V and 29 V, respectively NMR of His-cTCRf Results The protein was resuspended in 500 lL H2O and 50 lL D2O, and the pH adjusted to with dilute HCl Standard ... Chitu, V., Toth, G.K., Finta, C., Varadi, G., Ando, I ˆ & Monostori, E (1999) Contribution of kinases and the CD45 phosphatase to the generation of tyrosine phosphorylation patterns in the T-cell ... describe positions of the six ITAM tyrosines in TCRf and simulated trypsin digest of His-cTCRf The ITAM tyrosines have been named according to the ITAM they are in and their position within each...

Ngày tải lên: 08/03/2014, 02:20

... the expression (transcription, mRNA and protein levels), of both Rb and Sp1 after CDK inhibition by the chemical inhibitors UCN-01, roscovitine and olomoucine, and by the intrinsic inhibitor p21 ... Rb and Sp1 protein caused by CDK inhibitors in CHO cells The increase in total levels of Rb and Sp1 proteins caused by UCN-01 may be a result of the enhanced transcription and stability of Rb and ... CDK inhibitors First, the expression of Sp1 strongly increases with the chemical inhibitors UCN-01, roscovitine and olomoucine, and with the overexpression of the intrinsic inhibitor p21 Second, ...

Ngày tải lên: 16/03/2014, 23:20

... threonine and tyrosine kinases may have an important role to play in the physiology and pathogenesis of B anthracis In this article, for the first time we show the presence of an active tyrosine kinase ... putative tyrosine kinases in B subtilis, which include YwqD, YveL, SojA, SalA, MinD and McsB [5,9,10,13–16] However, only three proteins, YwqD [protein tyrosine kinase A (PtkA)], YveL [protein tyrosine ... tyrosine kinase A (PtkA)], YveL [protein tyrosine kinase B (PtkB)] and McsB have been reported to possess tyrosine kinase activity These tyrosine kinases have been shown to regulate various physiological...

Ngày tải lên: 23/03/2014, 06:20

... engagement and flow in the virtual reality, and increased their self-competence and self-efficacy Further, they experienced a sense of control and mastery over the virtual environment and perceived ... Journal of NeuroEngineering and Rehabilitation 2004, 1:9 (wall, obstacles, etc.) and social and cultural boundaries have a strong influence on the possibility of action and the quality of experience ... understand this point and in particular the difference between VR and other media, here are some examples [50]: Page of 11 (page number not for citation purposes) Journal of NeuroEngineering and...

Ngày tải lên: 19/06/2014, 10:20

... for protein kinase A, protein kinase C, or myosin light chain kinase, as well as over 20 times greater than that for two other downstream Rho effectors, citron kinase and protein kinase N [19,20] ... inhibitor of the serine/threonine kinases, PKA, PKC and MLCK The Ki values of H1152 for these kinases are about 390, 5800 and 6300 times higher than for Rho-kinases, respectively [21-23] H1152 ... Authors have read and approved the final manuscript Acknowledgements Prof K Actories and Prof D Meyer of the Institute of Experimental and Clinical Pharmacology and Toxicology, and Centre for Neuroscience,...

Ngày tải lên: 10/08/2014, 10:20

... beneficial in the treatment of both joint degeneration and pain associated with OA Materials and methods P38 kinase inhibitors The p38 kinase inhibitors SB 203580 and VX-745 were synthesized by the chemistry ... protein kinases (ERK), the c-Jun NH2-terminal kinase (JNK) and p38 http://www.journal-inflammation.com/content/5/1/22 [17] The p38 family has four members: α and β which are 75% homologous and γ and ... knee degeneration The the 1inhibitors SB-203580 and VX-745 significantly inhibThe p38 inhibitors SB-203580 and VX-745 significantly inhibited the severity of iodoacetate-induced knee degeneration...

Ngày tải lên: 11/08/2014, 08:22

... = standard deviation b 2531 (5.1) variables included in parent study8 Table Rate and Hazard Ratios of Treated Diabetes in Patients Exposed to Second- Generation Antipsychoticsa, By Doseb and Drug ... dataset, and have established data management and quality control checks A limited data set (defined by the Health Insurance Portability and Accountability Act (HIPAA) of 1996) was used and all ... corticosteroids, and valproate were most common, and 5% of patients were obese according to ICD-9 codes (Table 1) The rate and hazard ratios of treated diabetes in patients exposed to SGAs by dose and drug...

Ngày tải lên: 11/08/2014, 16:21

... Delusions, Hallucinatory behavior, Grandiosity, Suspiciousness/persecution, or Unusual thought content in the Positive and Negative Syndrome Scale (PANSS) [13], and were candidates for oral antipsychotic ... (CDSS) [16], and the Clinical Drug and Alcohol Use Scales (CDUS/ CAUS) [17], and were rated according to the Clinical Global Impression–Severity of Illness scale (CGI-S) [18], Page of 13 and the Global ... examinations, and laboratory tests The repeated physical examinations included Body Mass Index (BMI), waist and hip circumferences, and blood pressure Laboratory tests included electrocardiogram (ECG) and...

Ngày tải lên: 11/08/2014, 16:22

... spleen tyrosine kinase (Syk) protein Syk includes two tandem SH2 domains and a tyrosine kinase domain Interdomain A is between the two SH2 domains, and interdomain B is between the tyrosine kinase ... limited as it may inhibit additional kinases and non -kinase targets Among those targets are FMS-related tyrosine kinases (FLT3), Lck, and Janus kinase (JAK1) and JAK3, which may also be involved ... region tyrosines A mechanism for negative signaling by the Lyn tyrosine kinase J Biol Chem 2002, 277:31703-31714 15 Ghosh D, Tsokos GC: Spleen tyrosine kinase: an Src family of non-receptor kinase...

Ngày tải lên: 12/08/2014, 15:22

... yearly and radiographs of hands and feet were obtained in years to and year 10 The radiographs were evaluated for joint damage according to the Larsen scoring system [19,20] Analyses of sMer and ... Hafizi S, Dahlback B: Gas6 and protein S Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily FEBS J 2006, 273:5231-5244 Hafizi S, Dahlback B: Signalling and functional diversity ... receptor tyrosine kinases Cytokine Growth Factor Rev 2006, 17:295-304 Shao WH, Zhen Y, Eisenberg RA, Cohen PL: The Mer receptor tyrosine kinase is expressed on discrete macrophage subpopulations and...

Ngày tải lên: 12/08/2014, 15:23

... escape routes, the 2nd generation shRNAs G8A and G15A (Fig 1B) The gene cassettes encoding the primary shRNA-wt and the 2nd generation inhibitors shRNA-G8A and shRNA-G15A were individually cloned ... the 2nd generation shRNAs are active inhibitors and that they act in a sequence-specific manner HIV-1 inhibition studies with the 2nd generation shRNAs We next tested whether the 2nd generation ... mutated nucleotides to construct the 2nd generation shRNAs that target the G8A and G15A escape viruses (C) The primary shRNA-wt and the 2nd generation shRNA-G8A and shRNA-G15A cassettes were cloned...

Ngày tải lên: 13/08/2014, 01:20

... a mandatory switch to generic second- generation antihistamines: results of a patient survey in Norway Clinical and Molecular Allergy 2011 9:5 Submit your next manuscript to BioMed Central and ... the impact of a mandatory switch from one antihistamine to another Although the Norwegian Health Agency claimed that all second- generation antihistamines were equally efficacious and safe [8], 46.3% ... extrapolated to other groups of allergy patients, and any drug comparisons should be made with great caution Conclusions A mandatory switch to the generic second- generation antihistamines cetirizine or...

Ngày tải lên: 13/08/2014, 13:22

... broadcasting and related fields Since 1995 the JTC Broadcast became a tripartite body by including in the Memorandum of Understanding also CENELEC, which is responsible for the standardization of radio and ... Video Broadcasting (DVB); Second generation framing structure, channel coding and modulation systems for Broadcasting, Interactive Services, News Gathering and other broadband satellite applications ... A, B, or both 5.2.3.1 In-band type A An in-band signalling block carrying L1/L2 update information and co-scheduled information is defined as in-band type A When IN-BAND_ A_FLAG field in L1-post...

Ngày tải lên: 20/05/2015, 20:55

... passion and knowledge I am very grateful to Mr Alvin Kang Chiang Huen in Singapore and Dr Jaewon Cha in MIT for their mentorship They taught me all the knowledge and skills about optics hand by hand ... morphology and physiology with sub-cellular resolution viii and also dramatically improve the imaging speed In this thesis, the correlation of forward second harmonic generation (SHG) signal and backward ... while the third-ordered term gives rise to third harmonic generation and two-photon absorption We consider second harmonic generation and two-photon 17 CHAPTER BACKGROUND absorption processes...

Ngày tải lên: 09/09/2015, 08:17